Diastolic Dysfunction in Human Cardiac Allografts is Related with Reduced SERCA2a Gene Expression

• Published in: American journal of transplantation Vol. 6; no. 4; pp. 775 - 782
• Main Authors: Stüdeli, R., Jung, S., Mohacsi, P., Perruchoud, S., Castiglioni, P., Wenaweser, P., Heimbeck, G., Feller, M., Hullin, R.
• Format: Journal Article
• Language: English
• Published: Oxford UK Blackwell Publishing Ltd 01-04-2006; Blackwell
• Subjects: Adult; Aged; Biological and medical sciences; Calcium-Binding Proteins - genetics; Calcium-Transporting ATPases - genetics; Cardiac allograft; Cardiology. Vascular system; Collagen Type I - genetics; Desmin - genetics; Diastole - genetics; diastolic dysfunction; Down-Regulation - genetics; Exercise Tolerance - genetics; Gene Expression; Heart; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Heart Transplantation; Humans; Male; Medical sciences; Middle Aged; Myocardium - metabolism; Myocardium - pathology; Ryanodine Receptor Calcium Release Channel - genetics; Sarcoplasmic Reticulum Calcium-Transporting ATPases; SERCA2a; Sodium-Calcium Exchanger - genetics; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Ventricular Dysfunction, Left - diagnosis; Ventricular Dysfunction, Left - genetics; Heart; Human; Heart failure; Cardiac allograft; Cardiovascular disease; Transplantation; SERCA2a; Gene expression; Homotransplantation; Treatment; Dysfunction; Heart disease; Surgery; diastolic dysfunction; Graft; Circulatory system
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/j.1600-6143.2006.01241.x

Previous studies demonstrated that impaired left ventricular (LV) relaxation in cardiac allografts limits exercise tolerance post‐transplant despite preserved systolic ejection fraction (EF). This study tested in human cardiac allografts whether the isovolumic relaxation time (IVRT), which provides the basis for most of diastolic LV filling, relates with gene expression of regulatory proteins of calcium homeostasis or cardiac matrix proteins. Gene expression was studied in 31 heart transplant recipients (25 male, 6 female) 13–83 months post‐transplant with LVEF >50%, LV end‐diastolic pressure <20 mmHg, normal LV mass index and without allograft rejection or significant cardiac pathology. IVRT related with the other diastolic parameters e‐wave velocity (r=−0.46; p = 0.01), e/a‐wave ratio (r=−0.5; p < 0.01) but not with heart frequency (r=−0.16; p = 0.4). No relation of IVRT was observed for immunosuppression, mean rejection grade or other medication. IVRT was not related with gene expression of desmin, collagen I, phospholamban, the Na+‐Ca2+ exchanger, the ryanodine receptor or interstitial fibrosis but correlated inversely with SERCA2a (r=−0.48; p = 0.02). Prolonged IVRT is associated with decreased SERCA2a expression in cardiac allografts without significant other pathology. Similar observations in non‐transplanted patients with diastolic failure suggest that decreased SERCA2a expression is an important common pathomechanism.